Studies are being directed towards an understanding of the role of the products of the major histocompatibility complex in the cellular interactions of the immune response. Projects can be divided into three major categories: 1) Characterization of Major Histocompatibility Antigens: Congenic resistant strains of mice have been reciprocally immunized to produce antisera detecting the products of limited regions of the MHC. Antigens determined by genes in the Ir region termed Ia antigens have been detected and have been shown to provide a major source of stimulation of the MLC reaction; 2) Characterization of the Response to Major Histocompatibility Antigens: The effect of genetic background on the ability to respond to particular Ia and H-2 antigens is being assessed; and 3) Characterization of the Receptor Site for Histocompatibility Antigens: Anti-idiotypic antibodies are being produced and their effects on in vitro and in vivo parameters of graft rejection are being assessed. BIBLIOGRAPHIC REFERENCES: Schwartz, R.H., Fathman, C.G., and Sachs, D.H.: Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant. J. Immunol. 116: 929-935, 1976. Hansen, T., Cullen, S., and Sachs, D.H.: Immunochemical evidence for an additional H-2 region closely linked to H-2D. J. Exp. Med. 145: 438-442, 1977.